Electroencephalography (EEG) slowing and reduced functional connectivity are markers of Alzheimer's disease (AD) and Lewy body dementia (DLB), but the significance of epileptiform discharges to these changes remains unknown. We investigated whether epileptiform discharges are associated with EEG slowing or decreased functional connectivity over time. In this longitudinal observational exploratory study, 15 healthy controls, 25 patients with AD, and 10 patients with DLB were included. Patients underwent conventional resting-state EEG up to three times over 6 months, while baseline ear-EEG recording was used to quantify the number of epileptiform discharges per 24 hours. Compared with healthy controls, both patient groups showed a pattern of slowing and decreased alpha coherence. Epileptiform discharges were not associated with slowing or coherence at baseline. In longitudinal analyses, patients with DLB and epileptiform discharges demonstrated an increase in relative theta power over six months compared with patients with DLB without epileptiform discharges. No significant longitudinal theta-power changes were observed in patients with AD. These findings suggest that while EEG slowing is a characteristic feature of neurodegenerative diseases, epileptiform discharges are not directly associated with baseline EEG theta activity but may be linked to a distinct longitudinal trajectory of theta activity in DLB. Given the small group sizes and unbalanced subgroups analysis, these observations should be considered exploratory and require confirmation in larger longitudinal studies.

Epileptiform discharges in Alzheimer’s disease (AD) and Lewy body dementia (DLB) may be associated with cognitive decline. Iron accumulation has been implicated in neurodegenerative processes; however, its relationship to epileptiform discharges remains unknown. In addition, the relationship between iron deposition, structural brain changes, and epileptiform discharges remains unclear. The objective is to investigate whether iron deposition and structural brain atrophy are associated with epileptiform discharges in patients with AD, DLB, and healthy controls (HCs). A total of 25 patients with AD, 10 patients with DLB, and 15 HCs were included in the analysis. The participants underwent MRI including quantitative susceptibility mapping (QSM) and structural T1-weighted imaging. We examined the four regions of interest, which are tied to iron deposition and AD pathology. Ear-EEG recordings were used to quantify spike frequency (epileptiform discharges/24 h). No significant group differences were found for susceptibility across regions. Susceptibility was not associated with spike frequency. Patients with AD exhibited significant hippocampal atrophy. Higher hippocampal volume was associated with lower spike rates in adjusted models. Susceptibility and hippocampal volume were associated, and in a multilinear model with age, hippocampal volume accounted for a larger proportion of the explained variance. This study found no evidence linking iron deposition to epileptiform discharges in AD or DLB. Instead, hippocampal atrophy appears more strongly associated with epileptiform discharges, which could indicate that the underlying pathological processes rather than iron are the primary driving factor for epileptiform discharges.

Background: Studies have shown that quantitative EEG is useful in predicting conversion from mild cognitive impairment (MCI) to Alzheimer’s disease dementia (ADD) and dementia with Lewy bodies (DLB). As subcortical pathology is present and executive impairment is common in DLB, we hypothesized that EEG could predict conversion in patients with impaired executive function and any subcortical pathology. Methods: We included 113 patients with MCI from five Nordic memory clinics, 80 (71%) with amnestic MCI, 17 (15%) with dysexecutive MCI (deMCI), 3 (3%) with aphasic, 2 (2%) with visuospatial and 11 (10%) with unspecific MCI. Patients were examined with EEG in a resting state applying the statistical pattern recognition (SPR) method and followed up for five years. Eleven drop-outs were assessed after baseline. Receiver operating characteristic (ROC) analyses were used to examine the ability of EEG to predict conversion. Results: Sixty patients converted to dementia, 47 to ADD, eight to vascular dementia, two to DLB, one to frontotemporal dementia and two to unspecific dementia. Eight (11%) recovered and 45 (40%) remained MCI stable. ROC analyses revealed that EEG predicted conversion from dysexecutive MCI to dementia with area under the curve (AUC) of 0.92 (95% CI 0.76-100), sensitivity of 89% and specificity of 100%. Subcortical pathology was present in 89% of the dysexecutive MCI converters. EEG did not predict conversion from amnestic MCI to dementia. Conclusion: This study demonstrates that quantitative EEG using the SPR method predicts conversion from deMCI to dementia disorders with subcortical pathology with high sensitivity and specificity.

The Copenhagen Memory Clinic was established in 1995 and since 2007 a new national center for research and education was established, together forming the Danish Dementia Research Centre (DDRC). Our research and innovation programs have continuously been informed by clinical experience and inspired by the needs of our patients. The link between patient care, research, and education forming together a comprehensive dementia center is therefore of crucial importance. In this review, we present an overview of the clinical program at the Copenhagen Memory Clinic, currently receiving 2.000 new referrals per year. We also present the Copenhagen Memory Clinic Cohort and the associated biobank, as well as clinical, translational and epidemiological research programs performed at DDRC during the past 30 years. Funded in part by the Danish Ministry of Health, our national outreach, professional networks and educational programs are also outlined. From its inception and onwards the primary focus of the DDRC has been with the patients, aiming to continuously improve our clinical service based on research and innovation and to improve the quality of care nationwide. We welcome requests for collaboration on research, innovation and education from international colleagues and research centers.

Brain metabolism is reduced in patients with dementia disorders, as demonstrated by hypometabolism on 2-deoxy-2-[ 18 F]fluoroglucose ([ 18 F]FDG) positron emissions tomography. A contributing factor to the hypometabolism could be decreased cerebral blood flow (CBF) leading to a state of subtle hypoperfusion‐induced tissue hypoxia causing a reduced brain oxygen metabolism and consequently elevated brain lactate. In the current exploratory study, we investigated brain lactate, global and regional CBF, and global cerebral metabolic rate of oxygen (CMRO 2 ) in patients with Alzheimer’s disease (AD) and dementia with Lewy bodies (DLBs). We hypothesized that the patients demonstrate a state of tissue hypoxia with reduced CMRO 2 and elevated brain lactate concentration. Participants included 24 AD patients, 10 DLB patients, and 15 healthy controls. MR spectroscopy measured lactate in the precuneus and occipital lobe. Global CBF and venous oxygen saturation (for CMRO2 calculation) were assessed using phase-contrast and susceptibility-based oximetry MRI, respectively. Regional CBF was measured with ASL-MRI. We observed no significant difference in either brain lactate or CMRO 2 between groups. The regional CBF in precuneus was significantly lower in AD compared to HC; however, this hypoperfusion was not associated with a higher lactate concentration. The lack of a difference in CMRO 2 or lactate concentration between patients and controls suggests that the hypometabolism observed in patients with AD and DLB may reflect structural neurodegeneration and not a state of tissue hypoxia. The local decrease of CBF in precuneus in patients with AD may be due to a lower CBF demand due to neurodegeneration.

Introduction: Studies have shown that quantitative EEG is useful in predicting conversion from mild cognitive impairment (MCI) to Alzheimer's disease dementia (ADD) and dementia with Lewy bodies (DLBs). As subcortical pathology is present and executive impairment is common in DLB, we hypothesized that EEG could predict conversion in patients with impaired executive function and any subcortical pathology. Methods: We included 113 patients with MCI from 5 Nordic memory clinics, 80 (71%) with amnestic MCI, 17 (15%) with dysexecutive MCI (deMCI), 3 (3%) with aphasic, 2 (2%) with visuospatial, and 11 (10%) with unspecific MCI. Patients were examined with EEG in a resting state applying the statistical pattern recognition (SPR) method and followed up for 5 years. Eleven drop-outs were assessed after baseline. Receiver operating characteristic (ROC) analyses were used to examine the ability of EEG to predict conversion. Results: Sixty patients converted to dementia, 47 to ADD, 8 to vascular dementia, 2 to DLB, 1 to frontotemporal dementia, and 2 to unspecific dementia. Eight (11%) recovered, and 45 (40%) remained MCI stable. ROC analyses revealed that EEG predicted conversion from deMCI to dementia with area under the curve of 0.92 (95% CI 0.76-100), sensitivity of 89%, and specificity of 100%. Subcortical pathology was present in 89% of the deMCI converters. EEG did not predict conversion from amnestic MCI to dementia. Conclusion: This study demonstrates that quantitative EEG using the SPR method predicts conversion from deMCI to dementia disorders with subcortical pathology with high sensitivity and specificity.

Background In epilepsy, the ictal phase leads to cerebral hyperperfusion while hypoperfusion is present in the interictal phases. Patients with Alzheimer's disease (AD) have an increased prevalence of epileptiform discharges and a study using intracranial electrodes have shown that these are very frequent in the hippocampus. However, it is not known whether there is an association between hippocampal hyperexcitability and regional cerebral blood flow (rCBF). The objective of the study was to investigate the association between rCBF in hippocampus and epileptiform discharges as measured with ear-EEG in patients with Alzheimer's disease. Our hypothesis was that increased spike frequency may be associated with increased rCBF in hippocampus. Methods A total of 24 patients with AD, and 15 HC were included in the analysis. Using linear regression, we investigated the association between rCBF as measured with arterial spin-labelling MRI (ASL-MRI) in the hippocampus and the number of spikes/sharp waves per 24 h as assessed by ear-EEG. Results No significant difference in hippocampal rCBF was found between AD and HC (p-value = 0.367). A significant linear association between spike frequency and normalized rCBF in the hippocampus was found for patients with AD (estimate: 0.109, t-value = 4.03, p-value < 0.001). Changes in areas that typically show group differences (temporal-parietal cortex) were found in patients with AD, compared to HC. Conclusions Increased spike frequency was accompanied by a hemodynamic response of increased blood flow in the hippocampus in patients with AD. This phenomenon has also been shown in patients with epilepsy and supports the hypothesis of hyperexcitability in patients with AD. The lack of a significant difference in hippocampal rCBF may be due to an increased frequency of epileptiform discharges in patients with AD. Trial registration The study is registered at clinicaltrials.gov (NCT04436341).

BackgroundPatients with dementia with Lewy bodies (DLB) have a higher probability of seizures than in normal aging and in other types of neurodegenerative disorders. Depositions of & alpha;-synuclein, a pathological hallmark of DLB, can induce network excitability, which can escalate into seizure activity. Indicator of seizures are epileptiform discharges as observed using electroencephalography (EEG). However, no studies have so far investigated the occurrence of interictal epileptiform discharges (IED) in patients with DLB. ObjectivesTo investigate if IED as measured with ear-EEG occurs with a higher frequency in patients with DLB compared to healthy controls (HC). MethodsIn this longitudinal observational exploratory study, 10 patients with DLB and 15 HC were included in the analysis. Patients with DLB underwent up to three ear-EEG recordings, each lasting up to 2 days, over a period of 6 months. ResultsAt baseline, IED were detected in 80% of patients with DLB and in 46.7% of HC. The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with DLB as compared to HC with a risk ratio of 2.52 (CI, 1.42-4.61; P-value = 0.001). Most IED occurred at night. ConclusionsLong-term outpatient ear-EEG monitoring detects IED in most patients with DLB with an increased spike frequency compared to HC. This study extends the spectrum of neurodegenerative disorders in which epileptiform discharges occurs at an elevated frequency. It is possible that epileptiform discharges are, therefore, a consequence of neurodegeneration. & COPY; 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

In patients with Alzheimer’s disease (AD) without clinical seizures, up to half have epileptiform discharges in long-term in-patient electroencephalography (EEG) recordings. Long-term in-patient monitoring is obtrusive, and expensive as compared to out-patient monitoring. No studies have so far investigated if long-term out-patient EEG monitoring is able to identify epileptiform discharges in AD. To investigate if epileptiform discharges as measured with ear-EEG are more common in patients with AD compared to healthy elderly controls (HC). To understand the association with AD, we investigated the variability across multiple recordings. In this longitudinal observational study, 24 patients with mild to moderate AD and 15 age-matched HC were included in the analysis. Patients with AD underwent up to three ear-EEG recordings, each lasting up to two days, within 6 months. The first recording was defined as the baseline recording. At baseline, epileptiform discharges were detected in 75.0% of patients with AD and in 46.7% of HC (p-value = 0.073). The spike frequency (spikes or sharp waves/24 hours) was significantly higher in patients with AD as compared to HC with a risk ratio of 2.90 (CI: 1.77-5.01, p<0.001). Most patients with AD (91.7%) showed epileptiform discharges when combining all ear-EEG recordings. Long-term ear-EEG monitoring detects epileptiform discharges in most patients with AD with a three-fold increased spike frequency compared to HC, which most likely originates from the temporal lobes. Since most patients showed epileptiform discharges with multiple recordings, elevated spike frequency should be considered a marker of hyperexcitability in AD.

Introduction Aerobic exercise has been shown to modify Alzheimer pathology in animal models, and in patients with multiple sclerosis to reduce neurofilament light (NfL), a biomarker of neurodegeneration. Objective To investigate whether a 16-week aerobic exercise program was able to reduce serum NfL in patients with mild Alzheimer’s disease (AD). Methods This is a secondary analysis of data from the multi-center Preserving Cognition, Quality of Life, Physical Health, and Functional Ability in Alzheimer’s disease: The Effect of Physical Exercise (ADEX) study. Participants were randomized to 16 weeks of moderate intensity aerobic exercise or usual care. Clinical assessment and measurement of serum NfL was done at baseline and after the intervention. Results A total of 136 participants were included in the analysis. Groups were comparable at baseline except for APOEε4 carriership which was higher in the usual care group (75.3 versus 60.2%; p = 0.04). There was no effect of the intervention on serum NfL [intervention: baseline NfL (pg/mL) 25.76, change from baseline 0.87; usual care: baseline 27.09, change from baseline −1.16, p = 0.09]. Conclusion The findings do not support an effect of the exercise intervention on a single measure of neurodegeneration in AD. Further studies are needed using other types and durations of exercise and other measures of neurodegeneration. Clinical trial registration clinicaltrials.gov, identifier NCT01681602.

BACKGROUND:Previous studies have reported that epileptiform activity may be detectible in nearly half of patients with Alzheimer's disease (AD) on long-term electroencephalographic (EEG) recordings. However, such recordings can be uncomfortable, expensive, and difficult. Ear-EEG has shown promising results for long-term EEG monitoring, but it has not been used in patients with AD.OBJECTIVE:To investigate if ear-EEG is a feasible method for long-term EEG monitoring in patients with AD.METHODS:In this longitudinal, single-group feasibility study, ten patients with mild to moderate AD were recruited. A total of three ear-EEG recordings of up to 48 hours three months apart for six months were planned.RESULTS:All patients managed to wear the ear-EEG for at least 24 hours and at least one full night. A total of 19 ear-EEG recordings were performed (self-reported recording, mean: 37.15 hours (SD: 8.96 hours)). After automatic pre-processing, a mean of 27.37 hours (SD: 7.19 hours) of data with acceptable quality in at least one electrode in each ear was found. Seven out of ten participants experienced mild adverse events. Six of the patients did not complete the study with three patients not wanting to wear the ear-EEG anymore due to adverse events.CONCLUSION:It is feasible and safe to use ear-EEG for long-term EEG monitoring in patients with AD. Minor adjustments to the equipment may improve the comfort for the participants.

Background The two biomarkers 2-[ 18 F]FDG-PET and cerebrospinal fluid biomarkers are both recommended to support the diagnosis of Alzheimer’s disease. However, there is a lack of knowledge for the comparison of the two biomarkers in a routine clinical setting. Objective The aim was to compare the clinical impact of 2-[ 18 F]FDG-PET and cerebrospinal fluid biomarkers on diagnosis, prognosis, and patient management in patients suspected of Alzheimer’s disease. Methods Eighty-one patients clinically suspected of Alzheimer’s disease were retrospectively included from the Copenhagen Memory Clinic. As part of the clinical work-up all patients had a standard diagnostic program examination including MRI and ancillary investigations with 2-[ 18 F]FDG-PET and cerebrospinal fluid biomarkers. An incremental study design was used to evaluate the clinical impact of the biomarkers. First, the diagnostic evaluation was based on the standard diagnostic program, then the diagnostic evaluation was revised after addition of either cerebrospinal fluid biomarkers or 2-[ 18 F]FDG-PET. At each diagnostic evaluation, two blinded dementia specialists made a consensus decision on diagnosis, prediction of disease course, and change in patient management. Confidence in the decision was measured on a visual analogue scale (0–100). After 6 months, the diagnostic evaluation was performed with addition of the other biomarker. A clinical follow-up after 12 months was used as reference for diagnosis and disease course. Results The two biomarkers had a similar clinical value across all diagnosis when added individually to the standard diagnostic program. However, for the correctly diagnosed patient with Alzheimer’s disease cerebrospinal fluid biomarkers had a significantly higher impact on diagnostic confidence (mean scores±SD: 88±11 vs. 82±11, p = 0.046) and a significant reduction in the need for ancillary investigations (23 vs. 18 patients, p = 0.049) compared to 2-[ 18 F]FDG-PET. Conclusion The two biomarkers had similar clinical impact on diagnosis, but cerebrospinal fluid biomarkers had a more significant value in corroborating the diagnosis of Alzheimer’s disease compared to 2-[ 18 F]FDG-PET.

Introduction: The aim of this study was to examine if quantitative electroencephalography (qEEG) using the statistical pattern recognition (SPR) method could predict conversion to dementia in patients with subjective cognitive decline (SCD) and mild cognitive impairment (MCI). Methods: From 5 Nordic memory clinics, we included 47 SCD patients, 99 MCI patients, and 67 healthy controls. EEGs analyzed with the SPR method together with clinical data recorded at baseline were evaluated. The patients were followed up for a mean of 62.5 (SD 17.6) months and reexamined. Results: Of 200 participants with valid clinical information, 70 had converted to dementia, and 52 had developed Alzheimer’s disease. Receiver-operating characteristic analysis of the EEG results as defined by a dementia index (DI) ranging from 0 to 100 revealed that the area under the curve was 0.78 (95% CI 0.70–0.85), corresponding to a sensitivity of 71%, specificity of 69%, and accuracy of 69%. A logistic regression analysis showed that by adding results of a cognitive test at baseline to the EEG DI, accuracy could improve. Conclusion: We conclude that applying qEEG using the automated SPR method can be helpful in identifying patients with SCD and MCI that have a high risk of converting to dementia over a 5-year period. As the discriminant power of the method is of moderate degree, it should be used in addition to routine diagnostic methods.

Background Several factors may play a role in the ability of patients with Alzheimer’s disease to perform activities of daily living (ADL). The aim of this study was to examine the impact of different aspects of physical performance and cognitive functions on ADL in patients suffering from mild-to-moderate Alzheimer’s disease. Methods We conducted secondary analyses on cross-sectional baseline data from the randomized controlled multicentre study “Preserving quality of life, physical health and functional ability in Alzheimer’s Disease: The effect of physical exercise” (ADEX). In total, 185 AD patients (76 women and 109 men), with a mean age on 70,4 years, were included. Data from physical performance tests (Astrand cycle test, Timed up & Go (TUG), Sit to Stand test (STS)) and cognitive tests (Mini Mental Status Examination (MMSE), Symbol Digit Modalities Test (SDMT), Stroop Color and Word test (Stroop)) were used. Their associations with ADL, measured on the ADCS-ADL scale was assessed in multivariable regression analyses. Results SDMT and MMSE had significant, moderate correlations with total ADL (SDMT: r = 0.33, MMSE: r = 0.42) and instrumental ADL (SDMT: r = 0.31, MMSE: r = 0.42), but not with basic ADL. Adjusting for age and sex, the associations between SDMT and MMSE to total ADL and instrumental ADL persisted. No significant associations were found between Astrand, TUG, STS or Stroop and total ADL, basic ADL or instrumental ADL. Conclusion Total ADL and instrumental ADL are associated with cognitive functions, including executive function. No significant association between examined physical performance parameters and ADL functions was observed, and consequently does not support an impact of physical function on ADL functions in patients with mild-to-moderate Alzheimer’s disease and relatively well-preserved physical function. Strategies aimed to improve cognition may be better suited to improve ADL function in patients with mild-to-moderate Alzheimer’s disease. Trial registration NCT01681602 . Registered 10 September 2012, retrospectively registered.

Cholinergic dysfunction is central in Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). The electroencephalography-based acetylcholine index (EEG-Ach index) has been proposed as a biomarker of cho-linergic dysfunction. However, it is unclear how the EEG-Ach index relates to amyloid-beta pathology and neurodegeneration. We investigated the association between the EEG-Ach index and cerebrospinal fluid (CSF) amyloid-beta, CSF total tau, cortical thickness, and hippocampal volume from magnetic resonance imaging (MRI), and cognition. A total of 127 patients with different neurodegenerative diseases were studied. The EEG-Ach index was calculated from quantitative EEG using statistical pattern recognition. The EEG-Ach index was associated with hippocampal volume and cortical thickness in frontal, temporal, and occipital cortices. Cross-sectional sub-analyses based on a small sample suggests that the EEG-Ach index increases the closest to AD dementia, downstream to amyloid-beta pathology, CSF total tau, and hippocampal volume. We conclude that cholinergic dysfunction correlates with atrophy in brain areas important for AD pathogenesis, and this asso-ciation is more prominent in the dementia stage. These results together with previous studies from this project suggest that the EEG-Ach index may be a useful biomarker for cholinergic dysfunction, with value for differential diagnosis of dementia and monitoring patients at the dementia stage.

Lifestyle factors have been shown to increase the risk of developing Alzheimer's disease (AD) later in life. Specifically, an unfavorable cholesterol profile, and insulin resistance are associated with increased risk of developing AD. One way to non-pharmacologically affect the levels of plasma lipids is by exercise, which has been shown to be beneficial in cognitively healthy individuals. In this randomized controlled trial y, we therefore aimed to clarify the effect of physical exercise on the lipid profile, insulin and glucose in patients with AD. In addition, we investigated the effect of apolipoproteinE genotype on total cholesterol, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), and triglycerides (TG) in plasma from patients with AD. Plasma samples from 172 patients who underwent 16 weeks of moderate-to-high intensity exercise (n= 90) or treatment as usual (n= 82) were analyzed change from baseline for the levels of total cholesterol, LDL-C, HDL-C, TG, glucose, and insulin. In addition, we analyzed those from the exercise group who adhered to the protocol with an attendance of 2/3 or more of the exercise session and who followed the protocol of an intensity of 70% of the maximum heart rate. We found a significant increase in plasma HDL-C levels between the "high exercise sub-group" compared to control group. After intervention HDL-C was increased by 4.3% in the high-exercise group, and decreased by 0.7% in the control group, after adjustment for statin use. In conclusion, short term physical activity may be beneficial on the cholesterol profile in patients with AD.

Objectives Mild cognitive impairment (MCI) is associated with an increased risk of further cognitive decline, partly depending on demographics and biomarker status. The aim of the present study was to survey the clinical practices of physicians in terms of biomarker counseling, management, and follow-up in European expert centers diagnosing patients with MCI. Methods An online email survey was distributed to physicians affiliated with European Alzheimer's disease Consortium centers (Northern Europe: 10 centers; Eastern and Central Europe: 9 centers; and Southern Europe: 15 centers) with questions on attitudes toward biomarkers and biomarker counseling in MCI and dementia. This included postbiomarker counseling and the process of diagnostic disclosure of MCI, as well as treatment and follow-up in MCI. Results The response rate for the survey was 80.9% (34 of 42 centers) across 20 countries. A large majority of physicians had access to biomarkers and found them useful. Pre- and postbiomarker counseling varied across centers, as did practices for referral to support groups and advice on preventive strategies. Less than half reported discussing driving and advance care planning with patients with MCI. Conclusions The variability in clinical practices across centers calls for better biomarker counseling and better training to improve communication skills. Future initiatives should address the importance of communicating preventive strategies and advance planning.

Abstract Introduction Large‐scale brain networks are disrupted in the early stages of Alzheimer's disease (AD). Electroencephalography microstate analysis, a promising method for studying brain networks, parses EEG signals into topographies representing discrete, sequential network activations. Prior studies indicate that patients with AD show a pattern of global microstate disorganization. We investigated whether any specific microstate changes could be found in patients with AD and mild cognitive impairment (MCI) compared to healthy controls (HC). Materials and methods Standard EEGs were obtained from 135 HC, 117 patients with MCI, and 117 patients with AD from six Nordic memory clinics. We parsed the data into four archetypal microstates. Results There was significantly increased duration, occurrence, and coverage of microstate A in patients with AD and MCI compared to HC. When looking at microstates in specific frequency bands, we found that microstate A was affected in delta (1–4 Hz), theta (4–8 Hz), and beta (13–30 Hz), while microstate D was affected only in the delta and theta bands. Microstate features were able to separate HC from AD with an accuracy of 69.8% and HC from MCI with an accuracy of 58.7%. Conclusions Further studies are needed to evaluate whether microstates represent a valuable disease classifier. Overall, patients with AD and MCI, as compared to HC, show specific microstate alterations, which are limited to specific frequency bands. These alterations suggest disruption of large‐scale cortical networks in AD and MCI, which may be limited to specific frequency bands.

Valid diagnosis of dementia with Lewy bodies (DLB) is essential to establish appropriate treatment and care. However, the diagnostic accuracy is complicated by clinical and pathological overlap with Alzheimer's disease (AD). Cingulate island sign (CIS), defined as sparing of posterior cingulate cortex (PCC) relative to precuneus and cuneus on 18F-fluoro-deoxy-glucose positron emission tomography (18F-FDG-PET), is included in the revised diagnostic DLB criteria. There are no guidelines for the visual grading of CIS, although visual rating is a fast-applicable method in a clinical setting. The objective was to develop a robust visual CIS scale and evaluate the performance in differentiating DLB with and without amyloid beta pathology (A beta+/-), and AD. 18F-FDG-PET scans from 35 DLB patients, 36 AD patients, and 23 healthy controls were rated according to a visual CIS scale based on specific reading criteria. The visual CIS scale was validated against a quantitative CIS ratio derived from a region of interest analysis of PCC, precuneus, and cuneus. DLB patients had a significantly higher visual CIS score compared to AD patients, and controls. A cut-off visual CIS score of 4 significantly differentiated DLB A beta-patients from DLB A beta+ patients. In conclusion, the visual CIS scale is clinically useful to differentiate DLB from AD. The degree of CIS may be related to A beta pathology in DLB patients.

•The C9orf72 repeat expansion is a common cause of frontotemporal dementia.•Parkinsonism develops in a substantial number of patients with C9orf72 associated frontotemporal dementia.•C9orf72 associated frontotemporal dementia may be linked to mania and bipolar disease.